Bechmann I, Mor G, Nilsen J, Eliza M, Nitsch R, Naftolin F
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
Glia. 1999 Jul;27(1):62-74. doi: 10.1002/(sici)1098-1136(199907)27:1<62::aid-glia7>3.0.co;2-s.
Despite the mechanical blood-brain barrier, activated T-cells can cross brain vessels. Thus, the CNS is routinely surveyed by immune competent cells; yet the healthy brain is not a target of antigen-specific immune reactions. Therefore, mechanisms must exist to prevent brain-antigen-specific T-cells from inducing immune responses. Data indicate that activated T-cells entering the CNS may undergo apoptosis rather than leaving the brain to induce immune responses. Applying RT-PCR, Western-blots, and immunocytochemistry, we have demonstrated expression of the apoptosis-inducing protein Fas ligand on astrocytes and neurons of apparently normal rat and human brains. FasL-positive astrocytes were often situated in close vicinity to cerebral blood vessels in vivo and induced apoptosis of Fas expressing Jurkat cells in vitro. We propose that similar to other immune privileged organs FasL-induced apoptosis of activated T-cells in the brain protects the tissue from self damaging immune attacks by forming an immunological brain barrier.
尽管存在机械性血脑屏障，但活化的T细胞仍可穿越脑血管。因此，中枢神经系统会受到免疫活性细胞的常规监测；然而，健康的大脑并非抗原特异性免疫反应的靶标。所以，必然存在一些机制来阻止脑抗原特异性T细胞诱导免疫反应。数据表明，进入中枢神经系统的活化T细胞可能会发生凋亡，而不是离开大脑去诱导免疫反应。通过逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法和免疫细胞化学方法，我们已经证明在明显正常的大鼠和人类大脑的星形胶质细胞和神经元上存在诱导凋亡的蛋白Fas配体的表达。FasL阳性星形胶质细胞在体内常位于脑血管附近，并在体外诱导表达Fas的Jurkat细胞发生凋亡。我们提出，与其他免疫赦免器官类似，大脑中FasL诱导活化T细胞凋亡，通过形成免疫性脑屏障来保护组织免受自身免疫损伤攻击。
